The instant invention relates to oral drug compliance monitoring, and, more particularly, to the use of radio frequency identification tags ingested by the patient with a drug formulation.
Non-compliance of patients to drug regimens prescribed by their physicians results in increased cost of medical care, higher complication rates, as well as drug wastage. Non-compliance refers to the failure to take the prescribed dosage at the prescribed time which results in undermedication or overmedication. In a survey of 57 non-compliance studies, non-compliance ranged from 15% to as high as 95% in all study populations, regardless of medications, patient population characteristics, drug being delivered or study methodology (Greenberg, Clinical Therapeutics, 6(5):592-599, 1984).
In the clinical drug stage, accurately measuring compliance can lead to benefits such as: improved statistical reliability of a clinical study; clinical studies being completed sooner; and a determination of the effect of non-compliance as a function of the degree of non-compliance. In the therapeutic stage, accurately measuring compliance has a number of important benefits such as: warning a patient about the potential for developing a drug resistant infection related to poor compliance; and identifying a side effect of a drug related to overdosing.
Compliance to the instructions given to patients during any clinical trial is usually less than 50% in relatively short-term and less than 40% in longer-term trials using traditional methods (e.g., paper diaries) for making entries to show compliance (Vrijens and Goetghebeur, Statist. Med. 23, 531-544, 2004). A clinical trial on chronic pain patients reported only an 11% compliance with as high as 80% fake entries when paper diaries secretly instrumented to tract diary usage were given to patients (Stone et al., Control Clin. Trials. 24, 182-199, 2003) wherein on 32% of study days the paper diary was not opened, yet the compliance entries for those days exceeded 90%. A high incidence of intentional dumping of medications prior to the clinic visit by removing all or most of the medication at one time also occurs in clinical studies (Coutts et al, Arch. Dis. Child. 67, 332-333, 1992; Rand et al, Am. Rev. Respir. Dis. 146, 1559-1564, 1992; Rudd et al, Clin. Pharmacol. Therap. 46, 169-176, 1989; Simmons et al, Chest. 118, 290-295, 2000). Thus, deception among noncompliant patients occurs frequently in clinical trials, and is not often revealed by the traditional monitoring methods. The result is generation of data difficult to interpret and, worse, useless to reliably predict the effectiveness of clinical trials. Better monitoring of the time of actual drug intake will help alleviate many of these issues. For example, blood levels of a drug can be corrected for the time of actual drug intake for better pharmacokinetic/pharmacodynamic interpretations than relying on the time when patient(s) was instructed to take the medication. However, most of the present tracking devices that are utilized in clinical trials only track the initiation of the process of drug intake, i.e., by tracking the time the drug containers are opened or activated. In order to more accurately monitor the compliance of a clinical trial, a more sophisticated method of monitoring the drug intake is needed.
Confirmation of drug compliance by way of direct observation by trained persons is effective but impractical in most situations. Confirmation of drug compliance by blood or urine analysis is also impractical in most situations. Transdermal detection devices attached to the skin of a patient have been developed which detect ingested drug components through the skin and such devices can transmit a signal to a remote receiver at an external site such as a healthcare facility, see U.S. Pat. No. 6,663,846 and USPAP 2005/0031536. Electronic sensor systems have been developed which detect ingested drug components in the breath of a patient, see USPAP 2004/0081587. Radio frequency identification (RFID) tags have been incorporated into drug pills, each tag capable of identifying the type of medication, its dosage, and its lot number by way of a unique code emitted by the tag when interrogated by a corresponding radio frequency “reader”, see U.S. Pat. No. 6,366,206. The RFID of the '206 patent can incorporate a biosensor that detects, for example, a change in pH to determine whether the pill has dissolved and exposed the RFID tag to the environment of the gastrointestinal system. The technology of the '206 patent requires a highly specialized spherical RFID semiconductor and biosensor. It would be an advance in the art if RFID technology could be used in a less complex manner.